A hernia occurs when the content of a body cavity bulge out of the area where it is normally contained. There are many different types of hernias which are classified according to their anatomical location. The most common type of hernia is in the abdomen region, in which a weakness in the abdominal wall evolves into a localized hole, or a “defect”, through which abdominal organs may protrude.
Hernias usually need to be surgically repaired to prevent organ dysfunction and further complications. The repair is typically performed by reinforcing the muscle with surgical mesh prosthesis. Surgical complications may include surgical site infection, postoperative adhesions, bacterial contamination, hernia recurrence or chronic pain.
In recent years, fibrin glues are used increasingly in various clinical and surgical settings to decrease postoperative adhesion formation. In practice, the fibrin glue components are sprayed onto the operated site.
Fibrin glues are also known as fibrin sealants or fibrin adhesives. They are typically obtained by mixing a fibrinogen component and a thrombin component. Mixing both components mimics the physiological reaction of fibrin formation as it occurs in the blood circulation during the last step of the coagulation cascade, when thrombin converts the fibrinogen to fibrin by an enzymatic action. However, there is one major difference, the concentration of both fibrinogen and thrombin in the fibrin glue components are at least 20 times higher than their concentration in the plasma. For example, fibrinogen concentration in the plasma is about 2-3 mg/ml whereas fibrinogen concentration in the fibrin flue formulation is about 70-100 mg/ml. These attributes contribute to the physical nature and to the longevity of the formed clot.
The fibrinogen component may also contain other plasma proteins such as factor VIII, factor XIII, fibronectin, vitronectin and von willebrand factor. Some manufacturers add anti-proteolytic agents to the fibrin glue formulation (as described in WO-A-93/05822) or specifically remove the plasminogen in order to stop or delay the fibrinolysis (as described in U.S. Pat. No. 5,792,835 and U.S. Pat. No. 7,125,569). When the components are mixed the fibrin clot is formed and adheres to the application site. The physical properties of the fibrin sealant enables it to act as a fluid-tight sealing agent and stop bleeding and/or to seal tissues and surgical materials, such as graft, in a desired configuration. The tight fibrin structure, formed by a high concentration of thrombin, also forms a physical barrier that prevents infiltration of inflammatory cells, bacteria and omentum into the injured tissue consequently resulting in reduced local inflammatory reaction, reduced adhesion formation and reduced bacterial proliferation.
Martin-Cartes et al. (Sorg. Today 2008 38:135-140) discloses that a reduction in both the quantity and consistency of adhesions was observed in implanted prostheses covered with fibrin glue used in ventral hernia repair. In these studies the prostheses were placed at the site of surgery and covered with fibrin glue on the visceral side during the course of the surgical procedure. The draw back of spraying the fibrin glue onto a surgical mesh placed within the surgery area is that the process is time-consuming and is technically hard to perform while working through small incisions and under artificial lightening such as in laparoscopic procedure due to an inaccurate assessment of the thickness and the position of the fibrin glue on the surface of the mesh. In addition, the fibrin glue components can exit from the desired location either due to rinsing or surgeon error resulting in a relatively low volume of fibrin glue applied to the injured surface and in a non uniform layer of the applied material.
Fibrin glue pre-coated devices for vascular grafts have been disclosed. In these devices the fibrin coating is dry, present on the intraluminal side of the vascular graft and allows grow of endothelial cells inside the graft.
U.S. Pat. No. 5,272,074 provides methods for coating surfaces of polymeric materials with fibrinogen and fibrin through a process of heat denaturation. Described is that the adherence of fibrinogen to polymeric surfaces can be greatly enhanced by thermal denaturation of the D-domain of fibrinogen. It is disclosed that polymerized fibrin coated surfaces may be stabilized by treatment with thrombin, factor XIII and additional fibrinogen. It is indicated that the methods of coating are suitable for coating surfaces of prosthetic devices that are exposed to blood flow such as vascular grafts, artificial heart valves and cardiac assist device.
U.S. Pat. No. 5,660,873 is directed to a method for coating a surface of a substrate with fibrin. It is disclosed that the fibrin coated substrate is dried to yield a dried fibrin-coated substrate suitable for substrates that are exposed to blood flow such as intraluminal stents thereby creating devices with a low risk of inducing clot formation. The above patents are silent on a hernia mesh device.
US-A-2005/0010239 discloses a mesh device for surgical repair of hernia which contains a tissue adhesive. It is disclosed that the tissue adhesive within the mesh is activated after the mesh-device has been placed in the patient's body for securing the mesh in place without the need of sutures, staples or other securing apparatus.
WO 2009/019685 discloses a mesh comprising a first layer made of fibrin and allows cellular adhesion and a substantially non-porous second layer characterized by non-adhesion. In use the first layer is adhered to the tissue of the abdominal wall and enables wall tissues infiltration into the layer.
There is clearly an unmet need for a surgical prosthetic implant with reduced postoperative complications.